basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11466   1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11466   1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 24583320     64 NKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPTLPKNKKLSKAEILRLAIEYIKSLQEELQ 52

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein (HAND) family; The HAND family includes two bHLH transcription factors, HAND1 and HAND2. HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis. HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11466   1 RRGSANKKERRRTQSINSAFADLRECIPNVPADTKLSKIKTLRLATSYIAYLMDVL 56

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 1 (HAND1) and similar proteins; HAND1, also termed Class A basic helix-loop-helix protein 27 (bHLHa27), or extraembryonic tissues, heart, autonomic nervous system and neural crest derivatives-expressed protein 1 (eHAND), is a bHLH transcription factor that plays an essential role in both trophoblast-giant cells differentiation and in cardiac morphogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24583320  58 KKRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLDGD 117
Cdd:cd18952   1 RRKGAGPKKERRRTESINSAFAELRECIPNVPADTKLSKIKTLRLATSYIAYLMDVLAKD 60

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19686   1 QRQAANIRERKRMRSINDAFDGLRRHIPTFPYEKRLSKVDTLRLAIQYINFLTELL 56

basic helix-loop-helix (bHLH) domain found in twist-related protein 1 (TWIST1) and similar proteins; TWIST1, also termed Class A basic helix-loop-helix protein 38 (bHLHa38), or H-twist, is a bHLH transcriptional regulator that inhibits myogenesis by sequestrating E proteins, inhibiting trans-activation by MEF2, and inhibiting DNA-binding by MYOD1 through physical interaction. It also represses expression of proinflammatory cytokines such as TNFA and IL1B. In addition, TWIST1 is involved in cancer development and progression.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 24583320  50 PTSNTRIVKKRNTANKKERRRTQSINNAFSYLREKIPNVPTDtKLSKIKTLKLAILYINYLVNVLDGD-LDPK 121
Cdd:cd11412   3 PQSFEELQTQRVMANVRERQRTQSLNEAFAALRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLQSDeLDSK 74

basic helix-loop-helix (bHLH) domain found in twist-related protein (TWIST) family; The TWIST family includes TWIST1 and TWIST2, which are highly homologous bHLH transcription factors that promote epithelial-mesenchymal transition (EMT) during development and tumor metastasis. They are involved in the negative regulation of cellular determination and in the differentiation of several lineages, including myogenesis, osteogenesis, and neurogenesis. TWIST factors express in broad partially-overlapping patterns during embryo development and dimerize with a broad sets of dimer partners that form numerous unique transcriptional complexes to regulate embryonic development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDtKLSKIKTLKLAILYINYLVNVLDGD 117
Cdd:cd11464   1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLPSD-KLSKIQTLKLAARYIDFLYQVLRSD 58

basic helix-loop-helix (bHLH) domain found in pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is a bHLH transcription factor implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11417   1 QRQAANLRERRRMQSINDAFEGLRSHIPTLPYEKRLSKVDTLRLAIGYINFLSELV 56

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24583320  57 VKKRNTankKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11418   2 VARRNE---RERRRVQAVNDAFDRLRQHVPYLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

basic helix-loop-helix (bHLH) domain found in Caenorhabditis elegans Helix-loop-helix protein 13 (HLH13) and similar proteins; Caenorhabditis elegans HLH13, also termed Fer3-like protein, or nephew of atonal 3, is a bHLH transcription factor that plays a role in the negative regulation of exit from L1 arrest and dauer diapause dependent on IIS signaling (insulin and insulin-like growth factor (IGF) signaling).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11416   5 QRHAANIRERKRMLSINSAFEELRCHVPTFPYEKRLSKIDTLRLAIAYIALLRDIL 60

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L) and similar proteins; FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is a bHLH transcription factor expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24583320  57 VKKRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11415   7 YAQRQAANIRERRRMFNLNEAFDKLRKKVPTFAYEKRLSRIETLRLAIVYISFMTDLL 64

basic helix-loop-helix (bHLH) domain found in protein atonal homologs ATOH1, ATOH7 and similar proteins; The family includes ATOH1 and ATOH7. ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1). ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells. The family also includes protein Amos (also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein). It is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11430   1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGNDKKLSKYETLQMAQIYIETLSELL 56

basic helix-loop-helix (bHLH) domain found in factor in the germline alpha (FIGLA) and similar proteins; FIGLA, also termed FIGalpha, or Class C basic helix-loop-helix protein 8 (bHLHc8), or folliculogenesis-specific basic helix-loop-helix protein, or transcription factor FIGa, is a germ-cell-specific bHLH transcription factor expressed abundantly in female and less so in male germ cells. It is essential for primordial follicle formation and expression of many genes required for folliculogenesis, fertilization and early embryonic survival. FIGLA knockout mice cannot form primordial follicles and lose oocytes rapidly after birth, whereas male gonads are unaffected.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24583320  60 RNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11422   1 RRVANARERERVRNLNSGFSKLRRIVPLIPRDRKPSKVDTLKGATEYIRLLQRIL 55

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein Amos and similar proteins; Amos, also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein, is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24583320  58 KKRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19715   7 KRRLAANARERRRMNSLNVAFDKLRDVVPSLGDDRKLSKYETLQMAQSYITALKELL 63

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) and similar proteins; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19711   1 RRLESNERERQRMHKLNNAFQALREVIPHVRAEKKLSKIETLTLAKNYIKSLTTTI 56

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein taxi and similar proteins; Protein taxi, also termed protein delilah (Dei), is a bHLH transcription factor that is involved in regulation of cell adhesion and attachment that is expressed in specialized cells that provide anchoring sites to either muscles (tendon cells), or proprioceptors (chordotonal attachment cells) during embryonic development. It probably plays an important role in the differentiation of epidermal cells into the tendon cells that form the attachment sites for all muscles.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVP---TDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11431   1 RRKTANARERDRMREINDAFEALRRAVPEYPvagKDGKLTKITTLRLAMNYIKALTDLL 59

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 2 (TAL-2) and similar proteins; TAL-2, also termed Class A basic helix-loop-helix protein 19 (bHLHa19), is a bHLH transcription factor essential for the normal brain development. It has been implicated in T-cell acute lymphoblastic leukemia.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 24583320  64 NKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd19707   7 NTRERWRQQNVNSAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLVKLLG 58

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster helix loop helix protein 3B (dHLH3B) and similar proteins; Drosophila HLH3B is an uncharacterized bHLH transcription factor that belongs to the T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd19708   1 RRMFTNSRERWRQQNVNGAFAELRKLVPTHPPDKKLSKNEILRLAIKYIRLLSNVLE 57

basic helix-loop-helix (bHLH) domain found in musculin and similar proteins; Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. Musculin heterodimerizes with products of the E2A gene.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLDGD 117
Cdd:cd19703   4 QRNAANARERARMRVLSKAFSRLKTSLPWVPPDTKLSKLDTLRLASSYIAHLRQLLQED 62

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) family; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription. The family also includes Drosophila melanogaster protein dimmed and similar proteins. Dimmed, also termed DIMM, is a bHLH transcription factor that regulates neurosecretory (NS) cell function and neuroendocrine cell fate in Drosophila.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11426   1 RRLESNERERLRMHQLNDAFQALREVIPHVRSERKLSKIETLTLAKNYIKSLTNMI 56

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 1 (TAL-1) and similar proteins; TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-1 has been implicated in T-cell acute lymphoblastic leukemia. In common with other tissue-specific bHLH proteins, Tal heterodimerizes with ubiquitously-expressed members of the E2A family and form a DNA-binding complex with an E-box (CANNTG) to regulate transcription at its recognition site.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 24583320  57 VKKRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd19706   2 VVRRIFTNSRERWRQQNVNGAFAELRKLIPTHPPDKKLSKNEILRLAMKYINFLAKLLN 60

basic helix-loop-helix (bHLH) domain found in neurogenin (NGN) family; The NGN family includes three neural-specific bHLH transcription factors, NGN1-3, which may function at neuroblast selection genes during the development of several neuronal lineages. NGN-1, also termed Class A basic helix-loop-helix protein 6 (bHLHa6), or neurogenic basic-helix-loop-helix protein, or neurogenic differentiation factor 3 (NeuroD3), is a neural-specific bHLH transcription factor involved in the initiation of neuronal differentiation. NGN-2, also termed Class A basic helix-loop-helix protein 8 (bHLHa8), or protein atonal homolog 4 (ATOH4), is a neural-specific bHLH transcription factor required for sensory neurogenesis. NGN-3, also termed Class A basic helix-loop-helix protein 7 (bHLHa7), or protein atonal homolog 5 (ATOH5), is a neural-specific bHLH transcription factor expressed in the developing central nervous system and the embryonic pancreas. It is involved in neurogenesis and plays an important role in spermatogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd11428   1 RRLKANDRERNRMHNLNDALDALREVLPSFPDETKLTKIETLRFAHNYIWALSETLK 57

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins, achaete-scute-like proteins, ASCL1-2, and similar proteins; This subfamily includes Drosophila melanogaster AS-C proteins and two ASCL family of transcription factors, ASCL-1 and ASCL-2. Drosophila melanogaster AS-C proteins includes lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete scute homolog 1 (Mash1), is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete scute homolog 2 (Mash2), is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|.
gi 24583320  64 NKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19723   6 NERERNRVKLVNLGFATLREHVPNGRANKKMSKVETLRSAVEYIRQLQQLL 56

basic helix-loop-helix (bHLH) domain found in achaete-scute-like proteins, ASCL3-5, and similar proteins; This subfamily includes three ASCL family of transcription factors, ASCL-3, ASCL-4 and ASCL-5. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, may be involved in skin development. ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that is close related to ASCL-3 and ASCL-4.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24583320  57 VKKRNtanKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19724   2 IRKRN---ERERQRVRCVNEGYARLRRHLPLENKDKRLSKVETLRAAIRYIKHLQELL 56

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor (NeuroD) family; The NeuroD family includes NeuroD1, NeuroD2, NeuroD4 and NeuroD6. NeuroD1, also termed Class A basic helix-loop-helix protein 3 (bHLHa3), is a neuronal bHLH transcription factor involved in the development and maintenance of the endocrine pancreas and neuronal elements. It acts as an essential regulator of glutamatergic neuronal differentiation. Loss of NeuroD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. NeuroD2, also termed Class A basic helix-loop-helix protein 1 (bHLHa1), or NeuroD-related factor (NDRF), is a neuronal calcium-dependent bHLH transcription factor that induces neuronal differentiation and promotes neuronal survival. It plays a central role in thalamocortical synaptic maturation. NeuroD2 mediates calcium-dependent transcription activation by binding to E box-containing promoter. NeuroD4, also termed Class A basic helix-loop-helix protein 4 (bHLHa4), or protein atonal homolog 3 (ATH-3), or Atoh3, or Math-3, is a bHLH transcriptional activator that mediates neuronal differentiation. NeuroD6, also termed Class A basic helix-loop-helix protein 2 (bHLHa2), or protein atonal homolog 2 (ATH-2), or Atoh2, or Math2, or Nex1, is a neurogenic bHLH transcription factor involved in neuronal development, differentiation, and survival in Alzheimer's disease (AD) brains of both cohorts. It plays an integrative role in coordinating increase in mitochondrial mass with cytoskeletal remodeling, suggesting that it may act as a co-regulator of neuronal differentiation and energy metabolism.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24583320  60 RNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11427   1 RVKANARERNRMHGLNDALDNLRKVVPCYSKTQKLSKIETLRLARNYIWALSEIL 55

basic helix-loop-helix (bHLH) domain found in transcription factor 24 (TCF-24) and similar proteins; TCF-24 is an uncharacterized bHLH transcription factor that shows high sequence similarity with TCF-23.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24583320  60 RNTAnkKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19710   4 ANAA--RERSRVQTLRSAFLELQRTLPSVPPDTKLSKLDVLVLATTYIAHLMRTL 56

basic helix-loop-helix (bHLH) domain found in neurogenin-2 (NGN-2) and similar proteins; NGN-2, also termed Class A basic helix-loop-helix protein 8 (bHLHa8), or protein atonal homolog 4 (ATOH4), is a neural-specific bHLH transcription factor required for sensory neurogenesis. It activates transcription by binding to the E box (5'-CANNTG-3').

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19717  10 RRVKANNRERNRMHNLNAALDSLREVLPTFPEDAKLTKIETLRFAHNYIWALSETL 65

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 1 (ASCL-1) and similar proteins; ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 24583320  64 NKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd19742  10 NERERNRVKLVNMGFATLREHVPNGAANKKMSKVETLRSAVEYIRALQQLLD 61

basic helix-loop-helix (bHLH) domain found in neurogenin-3 (NGN-3) and similar proteins; NGN-3, also termed Class A basic helix-loop-helix protein 7 (bHLHa7), or protein atonal homolog 5 (ATOH5), is a neural-specific bHLH transcription factor expressed in the developing central nervous system and the embryonic pancreas. It is involved in neurogenesis and plays an important role in spermatogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19718   8 RRMKANDRERNRMHNLNSALDALRSVLPTFPDDAKLTKIETLRFAHNYIWALTETL 63

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 2 (ASCL-2) and similar proteins; ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 24583320  64 NKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVLDGDL 118
Cdd:cd19743   8 NERERNRVKLVNLGFAALRQHVPQGGASKKMSKVETLRSAVEYIRALQRLLGEHD 62

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in transcription factor AP-4 (TFAP4) and similar proteins; TFAP4, also termed activating enhancer-binding protein 4, or Class C basic helix-loop-helix protein 41 (bHLHc41), is a bHLHzip transcription factor that activates both viral and cellular genes involved in the regulation of cellular proliferation, stemness, and epithelial-mesenchymal transition by binding to the symmetrical DNA sequence 5'-CAGCTG-3'.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVpTDTKLSKIKTLKLAILYINYL 110
Cdd:cd11419   4 RREIANSNERRRMQSINAGFQSLRTLLPHC-DGEKLSKAAILQQTAEYIFSL 54

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster achaete-scute complex (AS-C) proteins and similar proteins; Drosophila melanogaster AS-C proteins includes lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 24583320  64 NKKERRRTQSINNAFSYLREKIPN-VPTDT----------KLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19744   6 NARERNRVKQVNNGFAILRQHIPQsVIEDLtagggrgkskKLSKVDTLRMAVEYIRRLQKLL 67

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 2 (NeuroD2) and similar proteins; NeuroD2, also termed Class A basic helix-loop-helix protein 1 (bHLHa1), or NeuroD-related factor (NDRF), is a neuronal calcium-dependent bHLH transcription factor that induces neuronal differentiation and promotes neuronal survival. It plays a central role in thalamocortical synaptic maturation. NeuroD2 mediates calcium-dependent transcription activation by binding to E box-containing promoter.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19720  35 RRQKANARERNRMHDLNSALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 90

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 22 (bHLHe22) and similar proteins; bHLHe22, also termed Class B basic helix-loop-helix protein 5 (bHLHb5), or trinucleotide repeat-containing gene 20 protein, is an OLIG-related bHLH neural-specific transcriptional repressor that is expressed in both excitatory (unipolar brush cells) and inhibitory neurons (cartwheel cells) of the dorsal cochlear nucleus (DCN) during development. It is important for the proper development and/or survival of a number of neural cell types.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24583320  60 RNTANKKERRRTQSINNAFSYLREKIP--NVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd18954   2 RLNINARERRRMHDLNDALDELRAVIPyaHSPSVRKLSKIATLLLAKNYILMQANALE 59

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein (SREBP) family; The SREBP family includes SREBP1 and SREBP2, which are bHLHzip transcriptional activator of genes encoding proteins essential for cholesterol biosynthesis/uptake and fatty acid biosynthesis. SREBP1 and SREBP2 are principally found in the liver and in adipocytes and made up of an N-terminal transcription factor portion (composed of an activation domain, a bHLHzip domain, and a nuclear localization signal), a hydrophobic region containing two membrane spanning regions, and a C-terminal regulatory segment. They recognize a symmetric sterol regulatory element (TCACNCCAC) instead of E-box.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 24583320  57 VKKRNTANKKERRRTQSINNAFSYLREKIpnVPTDTKLSKIKTLKLAILYINYLVNV 113
Cdd:cd11394   4 VEKRSAHNAIEKRYRSSINDRIIELKDLV--VGPDAKMNKSAVLRKAIDYIRYLQKV 58

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 1 (NeuroD1) and similar proteins; NeuroD1, also termed Class A basic helix-loop-helix protein 3 (bHLHa3), is a neuronal bHLH transcription factor involved in the development and maintenance of the endocrine pancreas and neuronal elements. It acts as an essential regulator of glutamatergic neuronal differentiation. Loss of NeuroD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 24583320  55 RIVKKRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd19719  24 RFKMRRMKANARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYIWALSEIL 83

basic helix-loop-helix (bHLH) domain found in Class A basic helix-loop-helix protein 9 (bHLHa9) and similar proteins; bHLHa9, also termed Class F basic helix-loop-helix factor 42 (bHLHf42), is a bHLH transcription factor that plays an essential role in limb development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd18912   8 RRVAANVRERKRILDYNQAFNALRLALKHDLGGKRLSKIATLRRAINRISALSLFL 63

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 23 (bHLHe23) and similar proteins; bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is an OLIG-related bHLH transcription factor that is expressed in rod bipolar cells and is required for rod bipolar cell maturation. bHLHe23 have roles in spinal interneuron differentiation by mechanisms linked to the Notch signaling pathway. It modulates the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 24583320  60 RNTANKKERRRTQSINNAFSYLREKIP--NVPTDTKLSKIKTLKLAILYINYLVNVLD 115
Cdd:cd18953   8 RLSINARERRRMHDLNDALDGLRSVIPyaHSPSVRKLSKIATLLLAKNYILMQAQALE 65

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in the Myc family; The Myc family is a member of the bHLHzip family of transcription factors that play important roles in the control of normal cell proliferation, growth, survival and differentiation. All Myc isoforms contain two independently functioning polypeptide chain regions: N-terminal transactivating residues and a C-terminal bHLHzip segment. The bHLHzip family of bHLH transcription factors are characterized by a highly conserved N-terminal basic region that may bind DNA at a consensus hexanucleotide sequence known as the E-box (CANNTG) followed by HLH and leucine zipper motifs that may interact with other proteins to form homo- and heterodimers. Myc heterodimerizes with Max enabling specific binding to E-box DNA sequences in the promoters of target genes. The Myc proto-oncoprotein family includes at least five different functional members: c-, N-, L-, S- and B-Myc (which is lacking the bHLH domain).

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPTDTKLSKIKTLKLAILYINYLVN 112
Cdd:cd11400   1 KRRLHNVLERQRRNDLKNSFEKLRDLVPELADNEKASKVVILKKATEYIKQLQQ 54

basic Helix-Loop-Helix-zipper (bHLHzip) domain found in sterol regulatory element-binding protein 2 (SREBP2) and similar proteins; SREBP2, also termed Class D basic helix-loop-helix protein 2 (bHLHd2), or sterol regulatory element-binding transcription factor 2 (SREBF2), is a member of a family of bHLHzip transcription factors that recognize sterol regulatory element 1 (SRE-1). It acts as a transcription activator of cholesterol biosynthesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  58 KKRNTANKKERRRTQSINNAFSYLREKIpnVPTDTKLSKIKTLKLAILYINYLVNV 113
Cdd:cd18922   5 ERRTTHNIIEKRYRSSINDKIIELKDLV--MGTDAKMHKSGVLRKAIDYIKYLQQV 58

basic helix-loop-helix (bHLH) domain found in myoblast determination protein 1 (MYOD1) and similar proteins; MYOD1, also termed Class C basic helix-loop-helix protein 1 (bHLHc1), or myogenic factor 3 (Myf-3), is a bHLH transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with Myf-5 and MYOG, MYOD1 co-occupies muscle-specific gene promoter core region during myogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPtDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd18936   6 RRKAATMRERRRLSKVNEAFETLKRCTSTNP-NQRLPKVEILRNAIRYIESLQALL 60

basic helix-loop-helix (bHLH) domain found in myogenic regulatory factor (MRF) family; MRFs are a family of muscle-specific bHLH transcription proteins (MyoD, Myf5, Mrf4 and MyoG) that plays an essential role in regulating skeletal muscle development and growth. MRFs are capable of binding to E-box motifs as a heterodimer with E-proteins to regulate transcription expression.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 24583320  59 KRNTANKKERRRTQSINNAFSYLREKIPNVPtDTKLSKIKTLKLAILYINYLVNVL 114
Cdd:cd11411   2 RRKAATMRERRRLKKVNEAFEALKRCTSANP-NQRLPKVEILRNAIEYIESLQDLL 56

basic helix-loop-helix (bHLH) domain found in Arabidopsis thaliana BES1-interacting Myc-like proteins (BIMs) and similar proteins; The family includes Arabidopsis thaliana BIM1 and its homologs (BIM2 and BIM3), which are bHLH transcription factors that interact with BES1 to regulate transcription of Brassinosteroid (BR)-induced gene. BR regulates many growth and developmental processes such as cell elongation, vascular development, senescence stress responses, and photomorphogenesis. BIM1 heterodimerize with BES1 and bind to E-box sequences present in many BR-induced promoters to regulated BR-induced genes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24583320  53 NTRIVKKRNTankkERRRTQSINNAFSYLREKIPNvpTDTKLSKIKTLKLAILYINYL---VNVLDGDLDPKGGFRAELK 129
Cdd:cd11453   1 STPRSKHSAT----EQRRRSKINERLQALRDLIPH--SDQKRDKASFLLEVIEYIQALqekVAKLEEQVQGWGGEPAKLT 74